Kodi S. Ravichandran

Education

  • BVSc, Madras Veterinary College, Madras, India
  • PhD, University of Massachusetts, Amherst, MA
  • Postdoc, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Primary Appointment

  • Professor and Chair, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Apoptotic cell clearance mechanisms in health and disease

Research Description

My laboratory has been addressing two main topics over the years: (i) The signals that regulate B and T cell development and function. In this regard, we use a combination of knockout and transgenic mice to address the developmental checkpoint that are in place to regulate T cell development and how they affect immune system function (ref #9,10 below). (ii) The molecules/mechanisms that regulate the process of apoptotic cell clearance. In this context, we address the different steps of the apoptotic cell engulfment process: how apoptotic cells advertise their presence to phagocytes (‘find-me signal’ release) (ref #7,8,16), how phagocytes recognize and ingest the apoptotic cells (eat-me signals and phagocytic receptors) (ref #1 to 6, and 14), and how the phagocytes digest the ingested corpses (ref #12,13,14). We are also interested in how the engulfment of apoptotic cells is immunologically silent (in contrast to other types of phagocytosis) and how this intersects and integrates with innate immune mechanisms (ref #15 and 16). We use knockout and transgenic mouse models, mammalian cell culture, drug screens, human samples, as well as genetic studies C. elegans.

Selected Publications

  • Poon I, Chiu Y, Armstrong A, Kinchen J, Juncadella I, Bayliss D, Ravichandran K. Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature. 2014;507(7492): 329-34. PMID: 24646995 | PMCID: PMC4078991
  • Hochreiter-Hufford A, Lee C, Kinchen J, Sokolowski J, Arandjelovic S, Call J, Klibanov A, Yan Z, Mandell J, Ravichandran K. Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature. 2013;497(7448): 263-7. PMID: 23615608 | PMCID: PMC3773542
  • Juncadella I, Kadl A, Sharma A, Shim Y, Hochreiter-Hufford A, Borish L, Ravichandran K. Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Nature. 2012. PMID: 23235830 | PMCID: PMC3662023
  • Park D, Han C, Elliott M, Kinchen J, Trampont P, Das S, Collins S, Lysiak J, Hoehn K, Ravichandran K. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011;477(7363): 220-4. PMID: 21857682 | PMCID: PMC3513690
  • Chekeni F, Elliott M, Sandilos J, Walk S, Kinchen J, Lazarowski E, Armstrong A, Penuela S, Laird D, Salvesen G, Isakson B, Bayliss D, Ravichandran K. Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature. 2010;467(7317): 863-7. PMID: 20944749 | PMCID: PMC3006164
  • Elliott M, Zheng S, Park D, Woodson R, Reardon M, Juncadella I, Kinchen J, Zhang J, Lysiak J, Ravichandran K. Unexpected requirement for ELMO1 in clearance of apoptotic germ cells in vivo. Nature. 2010;467(7313): 333-7. PMID: 20844538 | PMCID: PMC3773546
  • Kinchen J, Ravichandran K. Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells. Nature. 2010;464(7289): 778-82. PMID: 20305638 | PMCID: PMC2901565
  • Elliott M, Chekeni F, Trampont P, Lazarowski E, Kadl A, Walk S, Park D, Woodson R, Ostankovich M, Sharma P, Lysiak J, Harden T, Leitinger N, Ravichandran K. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461(7261): 282-6. PMID: 19741708 | PMCID: PMC2851546
  • Trampont P, Tosello-Trampont A, Shen Y, Duley A, Sutherland A, Bender T, Littman D, Ravichandran K. CXCR4 acts as a costimulator during thymic beta-selection. Nature immunology. 2009;11(2): 162-70. PMID: 20010845 | PMCID: PMC2808461
  • Kinchen J, Doukoumetzidis K, Almendinger J, Stergiou L, Tosello-Trampont A, Sifri C, Hengartner M, Ravichandran K. A pathway for phagosome maturation during engulfment of apoptotic cells. Nature cell biology. 2008;10(5): 556-66. PMID: 18425118 | PMCID: PMC2851549
  • Park D, Tosello-Trampont A, Elliott M, Lu M, Haney L, Ma Z, Klibanov A, Mandell J, Ravichandran K. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature. 2007;450(7168): 430-4. PMID: 17960134
  • Stites E, Trampont P, Ma Z, Ravichandran K. Network analysis of oncogenic Ras activation in cancer. Science (New York, N.Y.). 2007;318(5849): 463-7. PMID: 17947584
  • Lu M, Kinchen J, Rossman K, Grimsley C, deBakker C, Brugnera E, Tosello-Trampont A, Haney L, Klingele D, Sondek J, Hengartner M, Ravichandran K. PH domain of ELMO functions in trans to regulate Rac activation via Dock180. Nature structural & molecular biology. 2004;11(8): 756-62. PMID: 15247908
  • Brugnera E, Haney L, Grimsley C, Lu M, Walk S, Tosello-Trampont A, Macara I, Madhani H, Fink G, Ravichandran K. Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex. Nature cell biology. 2002;4(8): 574-82. PMID: 12134158
  • Zhang L, Camerini V, Bender T, Ravichandran K. A nonredundant role for the adapter protein Shc in thymic T cell development. Nature immunology. 2002;3(8): 749-55. PMID: 12101399
  • Gumienny T, Brugnera E, Tosello-Trampont A, Kinchen J, Haney L, Nishiwaki K, Walk S, Nemergut M, Macara I, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner M, Ravichandran K. CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration. Cell. 2001;107(1): 27-41. PMID: 11595183